The lung is a major organ for synthesis and metaboliism of a variety of vasoactive substances. Synthesis and release of products in the arachidonic acid cascade such as prostaglandins, prostacyclin (PGI2) and thromboxane A2 are enhanced in a number of lung disorders; however, the actions of all metabolites in the cascade have not been defined. Another goal of the proposed research project is to improve our understanding of the actions of a number of highly-active derivatives of arachidonic acid in the pulmonary vascular bed and systemic circulation. A second major goal of the proposed project is to determine if prostacyclin-like agents may be useful in the treatment of pulmonary hypertensive and thromboembolic disorders. Right heart and transseptal catheterization techniques will be used to maintain pulmonary blood flow constant in the intact chest animal. These techniques have recently been used to study responses in the intact chest cat and this species has proven to be highly sensitive and stable. Prostacyclin is the major product derived from endoperoxide intermediates and arachidonic acid in vascular tissue. Therefore, a third mauor goal of the proposed project is to define the actions of PGI2 and thromboxane A2, which is generated in certain pathologic states, in the systemic vascular bed. Moreover, the actions of PGI2 and inhibitors of prostacyclin synthesis on responses to sympathetic stimulation and pressor hormones will be investigated in the renal, mesenteric and hindlimb vascular beds. Overall experiments outlined in this proposal wwll improve our knowledge of the regulation of the pulmonary vascular bed and the peripheral vascular bed by vasoactive hormones. These studies may lead to new xxxxx of therapy for diseases such as pulmonary hypertension, bronchial asthma, thromboembolic disorders and essential hypertension.